Genetic Variant COMMD7:p.Glu43Gly (chr20-32728099-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053041.3(COMMD7):c.128A>G(p.Glu43Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

COMMD7
NM_053041.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

Variant links:

Genes affected

COMMD7 (HGNC:16223): (COMM domain containing 7) Enables NF-kappaB binding activity. Involved in negative regulation of NF-kappaB transcription factor activity; negative regulation of transcription, DNA-templated; and tumor necrosis factor-mediated signaling pathway. Predicted to be located in cytoplasmic vesicle. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

COMMD7 links:

ENSG00000285382 (HGNC:):

ENSG00000285382 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22850758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD7	NM_053041.3 link	c.128A>G	p.Glu43Gly	missense_variant	Exon 2 of 9	ENST00000278980.11	NP_444269.2	Q86VX2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD7	ENST00000278980.11 link	c.128A>G	p.Glu43Gly	missense_variant	Exon 2 of 9	1	NM_053041.3	ENSP00000278980.6		Q86VX2-1
ENSG00000285382	ENST00000646357.1 link	c.128A>G	p.Glu43Gly	missense_variant	Exon 2 of 9			ENSP00000493768.1		A0A2R8Y455

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.128A>G (p.E43G) alteration is located in exon 2 (coding exon 2) of the COMMD7 gene. This alteration results from a A to G substitution at nucleotide position 128, causing the glutamic acid (E) at amino acid position 43 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

.;.;T;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.063

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;D;T;T;D

M_CAP

Benign

0.0052

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;.;M;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.0

.;.;N;N;.

REVEL

Benign

0.078

Sift

Benign

0.12

.;.;T;T;.

Sift4G

Benign

0.28

.;.;T;T;.

Polyphen

0.0070, 0.011

.;.;B;B;.

Vest4

0.45, 0.50

MutPred

0.54

Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);.;Loss of solvent accessibility (P = 0.0477);

MVP

0.28

MPC

0.27

ClinPred

0.78

GERP RS

4.9

Varity_R

0.33

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over